Antimicrobial Activity of Neutrophils Against Mycobacteria

Abstract

The mycobacterium genus contains a broad range of species, including the human pathogens M. tuberculosis and M. leprae. These bacteria are best known for their residence inside host cells. Neutrophils are frequently observed at sites of mycobacterial infection, but their role in clearance is not well understood. In this review, we discuss how neutrophils attempt to control mycobacterial infections, either through the ingestion of bacteria into intracellular phagosomes, or the release of neutrophil extracellular traps (NETs). Despite their powerful antimicrobial activity, including the production of reactive oxidants such as hypochlorous acid, neutrophils appear ineffective in killing pathogenic mycobacteria. We explore mycobacterial resistance mechanisms, and how thwarting neutrophil action exacerbates disease pathology. A better understanding of how mycobacteria protect themselves from neutrophils will aid the development of novel strategies that facilitate bacterial clearance and limit host tissue damage.

Diagnostic Value of Neutrophil-to-Lymphocyte Ratio, Lymphocyte-to-Monocyte Ratio, and Platelet-to-Lymphocyte Ratio in the Diagnosis of Erythema Nodosum Leprosum: A Retrospective Study

“…Erythema nodosum leprosum (ENL) is an acute inflammatory complication of leprosy that exclusively occurs in MB leprosy [ 5 , 6 ]. It presents as a sudden onset of generalized painful erythematous nodules with or without symptoms of systemic inflammation that may occur before, during, or after multi-drug therapy (MDT) [ 6 , 7 , 8 ]. The clinical criteria proposed by B. Naafs et al for leprosy diagnosis are considered sufficient in daily clinical practice, although histopathological findings such as findings such as increased vascularity with dilated capillaries in the dermis with neutrophil infiltration may aid in disease confirmation [ 9 ].…”

“…ENL has frequent recurrence, with the possibility to persist for years [ 10 ]. Leprosy patients with ENL are prone to nerve damage and potential physical disabilities which severely impact their quality of life, the social and economic burden, and patients’ mortality [ 7 , 8 , 10 , 11 ]. The diagnosis of ENL often relies on the medical expertise of doctors and their ability to recognize the disease’s clinical manifestations [ 10 ].…”

Anti-tuberculosis treatment strategies and drug development: challenges and priorities

“…Second, polymorphonuclear leukocytes are increasingly recognized as a crucial and permissive niche of bacterial survival and replication 76 – 79 . Rather than eliminating mycobacteria, neutrophils seem to provide a safe haven and transport mycobacteria to macrophages while they retain the potential to damage host tissue 80 . To date, no in vivo or ex vivo assay has been developed to assess the drug tolerance of M. tuberculosis residing within and around neutrophils and other granulocytes.…”

Deficient Complement Opsonization Impairs Mycobacterium avium Killing by Neutrophils in Cystic Fibrosis

“…Neutrophils have been studied extensively in CF; however, their role against NTM infection in CF has been largely overlooked. Previous studies have investigated various aspects of neutrophil-mycobacterial interactions, including the role of phagocytosis, lysosomal killing, neutrophil extracellular traps (NETs), and neutrophil reactive oxygen species (ROS) with inconsistent findings, indicating a need for additional research ( 11 ). Relatively few studies have focused on M. avium , and the existing literature does not address whether there are differences in the context of CF.…”